Risk of newly detected infections and cervical abnormalities in adult women seropositive or seronegative for naturally acquired HPV-16/18 antibodies

Cancer Med. 2019 Aug;8(10):4938-4953. doi: 10.1002/cam4.1879. Epub 2019 Jul 5.


Background: Infections with human papillomavirus (HPV) types 16 and 18 account for ~70% of invasive cervical cancers but the degree of protection from naturally acquired anti-HPV antibodies is uncertain. We examined the risk of HPV infections as defined by HPV DNA detection and cervical abnormalities among women >25 years in the Human Papilloma VIrus Vaccine Immunogenicity ANd Efficacy trial's (VIVIANE, NCT00294047) control arm.

Methods: Serum anti-HPV-16/18 antibodies were determined at baseline and every 12 months in baseline DNA-negative women (N = 2687 for HPV-16 and 2705 for HPV-18) by enzyme-linked immunosorbent assay (ELISA) from blood samples. HPV infections were identified by polymerase chain reaction (PCR) every 6-months, and cervical abnormalities were confirmed by cytology every 12 months. Data were collected over a 7-year period. The association between the risk of type-specific infection and cervical abnormalities and serostatus was assessed using Cox proportional hazard models.

Results: Risk of newly detected HPV-16-associated 6-month persistent infections (PI) (hazard ratio [HR] = 0.56 [95%CI:0.32; 0.99]) and atypical squamous cells of undetermined significance (ASC-US+) (HR = 0.28 [0.12; 0.67]) were significantly lower in baseline seropositive vs baseline seronegative women. HPV-16-associated incident infections (HR = 0.81 [0.56; 1.16]) and 12-month PI (HR = 0.53 [0.24; 1.16]) showed the same trend. A similar trend of lower risk was observed in HPV-18-seropositive vs -seronegative women (HR = 0.95 [0.59; 1.51] for IIs, HR = 0.43 [0.16; 1.13] for 6-month PIs, HR = 0.31 [0.07; 1.36] for 12-month PIs, and HR = 0.61 [0.23; 1.61] for ASC-US+).

Conclusions: Naturally acquired anti-HPV-16 antibodies were associated with a decreased risk of subsequent infection and cervical abnormalities in women >25 years. This possible protection was lower than that previously reported in 15- to 25-year-old women.

Keywords: cervical abnormality; human papillomavirus infection; naturally acquired antibodies; redetection or reactivation of HPV infection; risk reduction.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Clinical Trials, Phase III as Topic
  • DNA, Viral / genetics
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / immunology*
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / immunology*
  • Humans
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / prevention & control
  • Proportional Hazards Models
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / virology


  • Antibodies, Viral
  • DNA, Viral

Associated data

  • ClinicalTrials.gov/NCT00294047